The Langkilde Lab in Action

What Makes Stress Stressful?

Stress is a familiar concept to most people. Paying the bills on time, entering a week of exams, caring for a sick loved one, or even sitting in heavy traffic on the way to work. When you get stressed out, your body goes through a series of changes to help you deal with that stress. This stress response includes both physiological and behavioral changes and is generally a good thing! For animals, the physiological stress response can mobilize energy and trigger important behavior, perhaps to get away from a predator. It can also enhance immune function in the short term to prepare for wounding or infection that might occur as a result of that stressful encounter.Short term stress is typically called “acute,” and the resulting stress response is very similar across vertebrates—because it works!

Stressors come in a variety of forms.

If stress lasts for a long time, however, there can be costs to using so much energy on the stress response. If you have ever become sick after a week of exams or a particularly challenging week at work, you know what I’m talking about. Long term stress—typically called “chronic” stress—can suppress immune function as well as growth and reproduction.

Sometimes, however, these generalizations don’t hold up—short term acute stress may produce negative consequences or long term chronic stress may produce positive outcomes. This got us wondering—just what is it about stress that might lead to negative consequences? We discuss just that in our latest paper published in General & Comparative Endocrinology, which is now available online.

Results published in GCE.

Stress is typically defined by duration—as acute or chronic— in the scientific literature as well as in veterinary and medical practices. I wanted to investigate not only stressor duration, but also other characteristics of the stressor, like frequency and intensity. There is some evidence that frequency and intensity affect the outcomes of stress, but few studies have attempted to look at how they might interact with each other or duration.

To test these ideas, I exposed fence lizards to different stress regimes. I did not want to use a physical stressor, so we instead manipulated a stress relevant hormone. When the stress response is activated, the glucocorticoid hormone cortisol (in humans) or corticosterone (in lizards) is secreted by the adrenal glands. We often measure CORT as a proxy for stress, and we can give a lizard CORT to replicate the increase in CORT that occurs in response to a stressor. After dissolving CORT in oil, one simply drops the solution onto the back of a lizard and it is quickly absorbed. One can also put the CORT-oil solution into a hormone patch for a slower release. These work a lot like a nicotine patch in humans, just with CORT and on a lizard.

A fence lizard with a slow release CORT patch. Stylish!

We used different regimes of CORT application to help determine how duration, frequency, and intensity affect immune outcomes in lizards. After the 9 days, we measured the innate immune system in two ways [similiar to this post], both of which roughly measure the ability of lizard blood to deal with foreign particles. One of these assess hemagglutination, which is the ability of plasma to hold sheep red blood cells in suspension. Higher scores indicate greater ability, or better immune function.

A completed hemagglutination assay.

Some of our results were particularly interesting:

Two of our treatments would be considered “acute.” Both were short in duration and differed only in the intensity of the dosage. Exposure to short duration low-doses of CORT enhanced immune function (hemagglutination), while exposure to short duration high-doses suppressed immune function. This indicates that intensity is an an important factor when considering immune outcomes of stress.This matches up with what we know about PTSD—short but intense stressors can have lasting effects in that context as well.

Additionally, while both of these treatments mimic “acute” stress, they produced opposite results. This demonstrates that the terms “acute” and “chronic” may not be enough to sufficiently characterize stress. These terms are also inconsistently used in the scientific literature, which only adds to the confusion.

Three of our treatments received the same average amount and total amount of CORT over each three day period and over the duration of the experiment but differed in how they were distributed–they varied in duration, intensity, and frequency. All three of these treatments, however, produced different outcomes—one enhanced immune function (frequent low doses), one suppressed immune function (infrequent high doses), and one was somewhere in the middle (slow release of the high dose). This suggests that average or total amount of stress (CORT) may not be comprehensive enough to characterize how the stress is experienced or accurately reflect its outcomes.

Although frequency and duration had lesser roles in this experiment, intensity was a major factor in altering the immune consequences of stress. We recommend that researchers consider and report aspects of stress other than duration, such as intensity and frequency, to aid our understanding of the consequences of stress. We should also move away from the terms “acute” and “chronic,” as they are inconsistency used and incompletely describe stress.

Because the environment is changing due to climate and human activities, wild animals will be exposed to new stressors or familiar ones more often. Determining what about stress leads to negative consequences is important to understand how species will respond to environmental change.

How will wild organisms respond to the stress of environmental change?